101 research outputs found
Engineering a family of synthetic splicing ribozymes
Controlling RNA splicing opens up possibilities for the synthetic biologist. The Tetrahymena ribozyme is a model group I self-splicing ribozyme that has been shown to be useful in synthetic circuits. To create additional splicing ribozymes that can function in synthetic circuits, we generated synthetic ribozyme variants by rationally mutating the Tetrahymena ribozyme. We present an alignment visualization for the ribozyme termed as structure information diagram that is similar to a sequence logo but with alignment data mapped on to secondary structure information. Using the alignment data and known biochemical information about the Tetrahymena ribozyme, we designed synthetic ribozymes with different primary sequences without altering the secondary structure. One synthetic ribozyme with 110 nt mutated retained 12% splicing efficiency in vivo. The results indicate that our biochemical understanding of the ribozyme is accurate enough to engineer a family of active splicing ribozymes with similar secondary structure but different primary sequences
Effect of Cyclosporine and Rifampin on the Pharmacokinetics of Macitentan, a Tissue-Targeting Dual Endothelin Receptor Antagonist
Macitentan is a dual endothelin receptor antagonist under phase 3 investigation in pulmonary arterial hypertension. We investigated the effect of cyclosporine (Cs) and rifampin on the pharmacokinetics of macitentan and its metabolites ACT-132577 and ACT-373898 in healthy male subjects. In addition, in vitro studies were performed to investigate interactions between macitentan and its active metabolite ACT-132577 with human organic anion-transporting polypeptides (OATPs). The clinical study (AC-055-111) was conducted as a two-part, one-sequence, crossover study. Ten subjects in each part received multiple-dose macitentan followed by multiple-dose co-administration of Cs (part A) or rifampin (part B). In the presence of Cs, steady-state area under the plasma concentration–time profiles during a dose interval (AUCτ) for macitentan and ACT-373898 increased 10% and 7%, respectively, and decreased 3% for ACT-132577. Steady-state AUCτ of macitentan and ACT-373898 in the presence of rifampin decreased 79% and 64%, respectively. For ACT-132577, no relevant difference in AUCτ between the two treatments was observed. Macitentan co-administered with Cs or rifampin was well tolerated. The complementary in vitro studies demonstrated no marked differences in uptake rates of macitentan and ACT-132577 between the wild-type and OATP over-expressing cells over the concentration range tested. Concomitant treatment with Cs did not have any clinically relevant effect on the exposure to macitentan or its metabolites, at steady-state. Concomitant treatment with rifampin reduced significantly the exposure to macitentan and its metabolite ACT-373898 at steady-state but did not affect the exposure to the active metabolite ACT-132577 to a clinically relevant extent
Report on the In-vehicle Auditory Interactions Workshop: Taxonomy, Challenges, and Approaches
Jeon M, Hermann T, Bazilinskyy P, et al. Report on the In-vehicle Auditory Interactions Workshop: Taxonomy, Challenges, and Approaches. In: Proceedings of the 7th International Conference on Automotive User Interfaces and Interactive Vehicular Applications - Automotive'UI 15. 2015: 1-5.As driving is mainly a visual task, auditory displays play a critical role for in-vehicle interactions.To improve in-vehicle auditory interactions to the advanced level, auditory display researchers and automotive user interface researchers came together to discuss this timely topic at an in-vehicle auditory interactions workshop at the International Conference on Auditory Display (ICAD).The present paper reports discussion outcomes from the workshop for more discussions at the AutoUI conference
Traffic and Related Self-Driven Many-Particle Systems
Since the subject of traffic dynamics has captured the interest of
physicists, many astonishing effects have been revealed and explained. Some of
the questions now understood are the following: Why are vehicles sometimes
stopped by so-called ``phantom traffic jams'', although they all like to drive
fast? What are the mechanisms behind stop-and-go traffic? Why are there several
different kinds of congestion, and how are they related? Why do most traffic
jams occur considerably before the road capacity is reached? Can a temporary
reduction of the traffic volume cause a lasting traffic jam? Under which
conditions can speed limits speed up traffic? Why do pedestrians moving in
opposite directions normally organize in lanes, while similar systems are
``freezing by heating''? Why do self-organizing systems tend to reach an
optimal state? Why do panicking pedestrians produce dangerous deadlocks? All
these questions have been answered by applying and extending methods from
statistical physics and non-linear dynamics to self-driven many-particle
systems. This review article on traffic introduces (i) empirically data, facts,
and observations, (ii) the main approaches to pedestrian, highway, and city
traffic, (iii) microscopic (particle-based), mesoscopic (gas-kinetic), and
macroscopic (fluid-dynamic) models. Attention is also paid to the formulation
of a micro-macro link, to aspects of universality, and to other unifying
concepts like a general modelling framework for self-driven many-particle
systems, including spin systems. Subjects such as the optimization of traffic
flows and relations to biological or socio-economic systems such as bacterial
colonies, flocks of birds, panics, and stock market dynamics are discussed as
well.Comment: A shortened version of this article will appear in Reviews of Modern
Physics, an extended one as a book. The 63 figures were omitted because of
storage capacity. For related work see http://www.helbing.org
A prototypical non-malignant epithelial model to study genome dynamics and concurrently monitor micro-RNAs and proteins in situ during oncogene-induced senescence
Mechanism of the Aromatic Hydroxylation of Thiophene by Acid-Catalyzed Peracid Oxidation
1,3-Dioxolane Formation by Nucleophilic Attack of Diazoalkanes on the Peroxide Bond of 1,2-Dioxetanes
Utilization of Synthetic Steel Gases in an Additively Manufactured Reactor for Catalytic Methanation
The path to European climate neutrality by 2050 will require comprehensive changes in all areas of life. For large industries such as steelworks, this results in the need for climate-friendly technologies. However, the age structure of existing steelworks makes transitional solutions such as carbon capture, utilization and storage (CCUS) necessary as short-term measures. Hence, a purposeful option is the integration of technical syntheses such as methanation into the overall process. This work summarizes hydrogen-intensified methanation experiments with synthetic steel gases in the novel additively manufactured reactor ‘ADDmeth1’. The studies include steady-state operating points at various reactor loads. Blast furnace gas (BFG), basic oxygen furnace gas (BOFG) and three mixtures of these two gases serve as carbon sources. The methanation achieved methane yields of 93.5% for BFG and 95.0% for BOFG in the one-stage once-through setup. The results suggest a kinetic limitation in the case of BFG methanation, while an equilibrium limitation is likely for BOFG. There is a smooth transition in all respects between the two extreme cases. The reaction channel inlet temperature ϑin showed a large influence on the reactor ignition behavior. By falling below the threshold value, a blow-off occurred during experimental operation. By means of a simulation model, practical operating maps were created which characterize permissible operating ranges for ϑin as a function of the gas composition and the reactor load
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